This invention relates to novel 1-benzyl and 1-phenyl-4-(2-hydroxy-3-benzyloxypropyl)-piperazines useful as immune regulants.
A number of compounds have been known in the art to be useful as anti-inflammatory agents, for example, the corticosteroids, phenylbutazone, indomethacin and various 3,4-dihydro-4-oxo-2H-1,2-benzothiazine-4-carboxamide-1,1-dioxides, such as those disclosed in U.S. Pat. No. 3,591,584. Accordingly, these compounds have been of therapeutic value in the treatment of arthritic and other inflammatory conditions such as rheumatoid arthritis. Such conditions have also been treated by administration of immuno-regulatory agents, such as levamisole, as described for example, in Arthritis Rheumatism, 20, 1445 (1977) and Lancet, 1, 393 (1976).
It is also known that biological vaccines such as Corynebacterium pavrum and BCG, a viable strain of Mycobacterium bovis, have utility as immune stimulants of the reticulo-endothelial system and are thereby capable of increasing the resistance of a warm blooded animal to tumors. However, the use of these agents has been restricted by hepatic-renal toxicity, granuloma formation, neutropenia and inconsistent therapeutic effects. Accordingly, it has been of continuing interest to develop non-biological, systemically active immune stimulants for use in increasing the resistance of a host to tumors. For discussions of the stimulation of cell-mediated immunity and antitumoral activity, see Herberman, Adv. Cancer Res., 19, 207 (1971), Jordan and Merigan, Ann. Rev. Pharmacol. 15, 157 (1975), Levy and Wheelock, Adv. Cancer Res., 20, 131 (1972) and Sinkovics, Post Graduate Medicine, 59, 110 (1976).